US2429244A - 1-d-ribitylamino-3,4-xylol and process for the manufacture of same - Google Patents

1-d-ribitylamino-3,4-xylol and process for the manufacture of same Download PDF

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US2429244A
US2429244A US626569A US62656945A US2429244A US 2429244 A US2429244 A US 2429244A US 626569 A US626569 A US 626569A US 62656945 A US62656945 A US 62656945A US 2429244 A US2429244 A US 2429244A
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parts
boric acid
xylol
ribitylamino
ribose
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US626569A
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Spiegelberg Hans
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F Hoffmann La Roche AG
Hoffmann La Roche Inc
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F Hoffmann La Roche AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical

Definitions

  • 1-d-ribitylamino-3,4-xylol' is an intermediate product for the preparation of lactoflavine (vitamin B2).
  • vitamin B2 lactoflavine
  • d-ribose is a very difficultly obtainable sugar; all the trouble arising during the manufacture of solid, crystalline ribose, consequent to the high solubility thereof, considerably increases the cost of the manufacture of the said compound and, consequently, of the manufacture of synthetic lactoflavine.
  • the intermediate product formed in the first reaction step is a boric acid compound of the condensation product of d-ribose with 3,4-dimethylaniline; it is a colorless, crystalline substance which, on heating, turns brown at 150 C. and decomposes completely at 183 C. According to the analysis, the compound is considered to correspond to the elementary formula C13H1sO5NB.
  • a solution of d-ribose in water or another solvent miscible with water as, for instance, alcohol, acetone, or mixtures thereof.
  • This solution may be crude; there is no need to purify the same by eliminating other sugars which may be present from the preparation of the ribose.
  • the mixture is set acid so as to have a uI-I of about 4.
  • the catalytic hydrogenation will preferably be carried out in the presence of an alcoholic solvent, such as, for instance, methyl or ethyl alcohol, and at a temperature substantially not exceeding 60 C.
  • Raney nickel or palladium charcoal may be used. After hydrogenation the boric acid is less tightly bound and can easily be eliminated during the working up.
  • the main advantage of the new process lies in the 'fact that the troublesome isolation of d-ribose from its solutions, which entails great losses, can be avoided, even if the solutions contain other sugars, such as, for instance, d-arabinose.
  • Example 1 62 parts by weight of boric acid are dissolved in a solution of 150 parts by weight of d-ribosein 700 parts of water at 40-45 C. The mixture is cooled down to room temperature and reacted. with a solution of 122 parts by weight of 3,4- dimethylaniline in 400 parts by volume of alcohol by stirring. After about 1 or 2 minutes the crystallisation of the boric acid compound begins. For completion of crystallisation the mixture is cooled for 2 hours at 0 C. and then the solid substance separatedfrom the liquid. The precipitate is washed with 250 parts by volume of cold methyl alcohol. and 1000 parts by volume of ether and then dried in vacuo at normal temperature. 260 parts by weight of the boric acid compound of the condensation product of d-ribose with 3,4-dimethylaniline are obtained.
  • the boric acid compound is suspended in 900 parts by volume of methyl alcohol and hydrogenated by means of parts by weight of Raney nickel at a hydrogen-pressure of 30 atmospheres and a starting-temperature of 35 C.
  • the hydrogenation proceeds Very quickly under evolution of heat whereby the temperature rises to 60 C. This temperature is maintained for one hour.
  • the methyl alcohol is then driven off with steam. on cooling, the crude ribitylamino-xylol, which still contains some boric acid, crystallises from the aqueous solution.
  • the ribitylamino-xylol is dissolved in 3 N aqueous hydrochloric acid, the solution is decolorised by means of charcoal and adjusted with concentrated ammonia to pH 5 by stirring, whereby 190 to 200 parts by weight of pure 1-d-ribitylamino-3,4-xylol of melting point 142 C. crystallise out.
  • Example 2 v 600 parts by volume of acetone are added to a solution of parts by weight of d-ribose in 600 parts by weight of water. 62 parts by weight of boric acid are dissolved in this solution at room temperature. 122 parts by weight of melted 3,4- dimethyl-aniline are admixed and, after a short while, th boric acid compound of the condensation product of d-ribose with xylidin crystallises out. In order to complete the crystallisation, the mixture is left to stand at 0 C. for 2 hours. The boric acid compound is separated, washed with 250 parts by volume of acetone and 250 parts by volume of ether and dried in vacuo,
  • Example 3 124 parts by weight of boric acid are dissolved in a solution of 150 parts by weight of d-ribose and 150 parts by Weight of d-arabinose in 1500 parts of water at 40 C. After cooling down to and 1000 parts by volume of ether, whereupon, after drying in vacuo, 265 parts by weight of the boric acid compound of the condensation product of d-ribose with 3,4-dimethylaniline are I obtained, Whereas no such precipitate is formed with the d-arabinose. On working up of the boric acid compound in accordance with Example 1, 190 parts by weight of 1-d-ribitylamino-3,4-xylol of melting point 142 C. are obtained.
  • Example 4 3000 parts by weight of water as electrolyte in separated electrode rooms. The solution is then concentrated to 1200 parts by volume and the main part of the sodium sulfate is precipitated with 2000 parts by volume of alcohol and sucked off. The filtrate, which is concentrated to 1200 parts by volume, contains, apart from d-ribose, d-ribonic acid, adonite, excess boric acid and sodium sulfate. V
  • Process for the manufacture of l-d-ribitylamino-SA-xylol comprising reacting an aqueous solution of d-ribose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and catalytically hydrogenating the compound obtained.
  • Process for the manufacture of l-d-ribitylamino-3,4-xylol comprising reacting, at a pH of about 4, an aqueous solution of d-ribose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylani1ine and 'catalytically hydrogenating the compound obtained.
  • Process for the manufacture of l-d-ribitylamino-3,4-xylol comprising reacting an aqueous solution of d-ri-bose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and catalytically hydrogenating the compound obtained in the presence of an alcoholic solvent.
  • Process for the manufacture of l-d-ribitylamino-3,4-xylol comprising reacting an aqueous solution of d-ribose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and catalytically hydrogenating the compound obtained at a temperature not exceeding C.
  • Process for the manufacture of l-d-ribitylamino-SA-xylol comprising reacting an aqueous solution of d-ribose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and hydrogenating the compound obtained while using a substance selected from the group consisting of Raney nickel and palladium charcoal as catalyst.

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Description

Patented Oct. 21, 1947 1-d-RIBITYLAMINO-3 ESS FOR THE MAN Hans Spiegelberg, Basel, Hoffmann-La Roche poration of New Jersey Application November 3, 1945,
No Drawing.
,4-XYLOL AND PROCe UFACTURE OF SAME Switzerland, assignor to Inc., Nutley, N. J., a cor- Serial No. 626,569. In Switzerland November 7 Claims.
1-d-ribitylamino-3,4-xylol' is an intermediate product for the preparation of lactoflavine (vitamin B2). According to the methods hitherto known for th preparation of the said intermediate product it is necessary to start from solid, crystalline d-ribose. However, d-ribose is a very difficultly obtainable sugar; all the trouble arising during the manufacture of solid, crystalline ribose, consequent to the high solubility thereof, considerably increases the cost of the manufacture of the said compound and, consequently, of the manufacture of synthetic lactoflavine.
It has now been found that l-d-ribitylamino- 3,4-xylol can be obtained more easily by reacting d-ribose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and catalytically hydrogenating the compound obtained.
The intermediate product formed in the first reaction step is a boric acid compound of the condensation product of d-ribose with 3,4-dimethylaniline; it is a colorless, crystalline substance which, on heating, turns brown at 150 C. and decomposes completely at 183 C. According to the analysis, the compound is considered to correspond to the elementary formula C13H1sO5NB.
For carrying out the process it is advantageous to use a solution of d-ribose in water or another solvent miscible with water, as, for instance, alcohol, acetone, or mixtures thereof. This solution may be crude; there is no need to purify the same by eliminating other sugars which may be present from the preparation of the ribose. Preferably, the mixture is set acid so as to have a uI-I of about 4. The catalytic hydrogenation will preferably be carried out in the presence of an alcoholic solvent, such as, for instance, methyl or ethyl alcohol, and at a temperature substantially not exceeding 60 C. As catalysts Raney nickel or palladium charcoal may be used. After hydrogenation the boric acid is less tightly bound and can easily be eliminated during the working up.
The main advantage of the new process lies in the 'fact that the troublesome isolation of d-ribose from its solutions, which entails great losses, can be avoided, even if the solutions contain other sugars, such as, for instance, d-arabinose.
Example 1 62 parts by weight of boric acid are dissolved in a solution of 150 parts by weight of d-ribosein 700 parts of water at 40-45 C. The mixture is cooled down to room temperature and reacted. with a solution of 122 parts by weight of 3,4- dimethylaniline in 400 parts by volume of alcohol by stirring. After about 1 or 2 minutes the crystallisation of the boric acid compound begins. For completion of crystallisation the mixture is cooled for 2 hours at 0 C. and then the solid substance separatedfrom the liquid. The precipitate is washed with 250 parts by volume of cold methyl alcohol. and 1000 parts by volume of ether and then dried in vacuo at normal temperature. 260 parts by weight of the boric acid compound of the condensation product of d-ribose with 3,4-dimethylaniline are obtained.
The boric acid compound is suspended in 900 parts by volume of methyl alcohol and hydrogenated by means of parts by weight of Raney nickel at a hydrogen-pressure of 30 atmospheres and a starting-temperature of 35 C. The hydrogenation proceeds Very quickly under evolution of heat whereby the temperature rises to 60 C. This temperature is maintained for one hour. The methyl alcohol is then driven off with steam. on cooling, the crude ribitylamino-xylol, which still contains some boric acid, crystallises from the aqueous solution. In order to separate the boric acid, the ribitylamino-xylol is dissolved in 3 N aqueous hydrochloric acid, the solution is decolorised by means of charcoal and adjusted with concentrated ammonia to pH 5 by stirring, whereby 190 to 200 parts by weight of pure 1-d-ribitylamino-3,4-xylol of melting point 142 C. crystallise out.
Example 2 v 600 parts by volume of acetone are added to a solution of parts by weight of d-ribose in 600 parts by weight of water. 62 parts by weight of boric acid are dissolved in this solution at room temperature. 122 parts by weight of melted 3,4- dimethyl-aniline are admixed and, after a short while, th boric acid compound of the condensation product of d-ribose with xylidin crystallises out. In order to complete the crystallisation, the mixture is left to stand at 0 C. for 2 hours. The boric acid compound is separated, washed with 250 parts by volume of acetone and 250 parts by volume of ether and dried in vacuo,
Yield; 245 parts by weight. On the further working up of the boric acid compound in accordance with Example 1, to parts by weight of 1-d-ribitylamino-3,4-xylol are obtained.
Example 3 124 parts by weight of boric acid are dissolved in a solution of 150 parts by weight of d-ribose and 150 parts by Weight of d-arabinose in 1500 parts of water at 40 C. After cooling down to and 1000 parts by volume of ether, whereupon, after drying in vacuo, 265 parts by weight of the boric acid compound of the condensation product of d-ribose with 3,4-dimethylaniline are I obtained, Whereas no such precipitate is formed with the d-arabinose. On working up of the boric acid compound in accordance with Example 1, 190 parts by weight of 1-d-ribitylamino-3,4-xylol of melting point 142 C. are obtained.
Example 4 3000 parts by weight of water as electrolyte in separated electrode rooms. The solution is then concentrated to 1200 parts by volume and the main part of the sodium sulfate is precipitated with 2000 parts by volume of alcohol and sucked off. The filtrate, which is concentrated to 1200 parts by volume, contains, apart from d-ribose, d-ribonic acid, adonite, excess boric acid and sodium sulfate. V
The solution obtained as described above is adjusted by means of 3N bicarbonate of soda and bromo-phenol-blue as an indicator to pH 4 and reacted with 135 parts by weight of 3,4-dimethylaniline while stirring; in order to complete crystallisation, the mixture is kept at C. for 12 hours, After suction-filtration the precipitate is washed with acetone and methyl alcohol and the damp methyl alcoholic boric acid compound of the condensation product of d-ribose with Xylidine is hydrogenated in 900 parts by volume of methyl alcohol with 90 parts by weight of Raney nickel at a hydrogen pressure of 30 atmospheres and a temperature of 30-60 C. The further working up is effected in accordance with Example 1. Yield: 200 to 220 parts by weight of 1-d-ribityl-amino-3,4-xylol of melting point 142 C.
I claim:
1. Process for the manufacture of l-d-ribitylamino-SA-xylol, comprising reacting an aqueous solution of d-ribose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and catalytically hydrogenating the compound obtained.
2. Process for the manufacture of l-d-ribitylamino-3,4-xylol, comprising reacting a solution containing d-ribose in a solvent miscible with water, in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and catalytically hydrogenating the compound obtained.
3. Process for the manufacture of l-d-ribitylamino-3,4-xylol, comprising reacting, at a pH of about 4, an aqueous solution of d-ribose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylani1ine and 'catalytically hydrogenating the compound obtained.
4. Process for the manufacture of l-d-ribitylamino-3,4-xylol, comprising reacting an aqueous solution of d-ri-bose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and catalytically hydrogenating the compound obtained in the presence of an alcoholic solvent.
5. Process for the manufacture of l-d-ribitylamino-3,4-xylol, comprising reacting an aqueous solution of d-ribose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and catalytically hydrogenating the compound obtained at a temperature not exceeding C.
6. Process for the manufacture of l-d-ribitylamino-SA-xylol, comprising reacting an aqueous solution of d-ribose in the presence of at least 1 mol of boric acid with 1 mol of 3,4-dimethylaniline and hydrogenating the compound obtained while using a substance selected from the group consisting of Raney nickel and palladium charcoal as catalyst. v
7. The d-ribose-SA-dimethylaniline-borio acid complex of the formula C13H1805NB having a nitrogen content of 5.14 per cent and decomposing at 183 C.
US626569A 1944-11-24 1945-11-03 1-d-ribitylamino-3,4-xylol and process for the manufacture of same Expired - Lifetime US2429244A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0020959A1 (en) * 1979-06-08 1981-01-07 MERCK PATENT GmbH Process for the preparation of riboflavin
US4271290A (en) * 1978-06-15 1981-06-02 A.E.C. Societe De Chimie Organique Et Biologique 3,4-Xylidine-N-ribityl
US4360669A (en) * 1980-08-08 1982-11-23 Basf Aktiengesellschaft Preparation of N-(D)-ribityl-2-phenylazo-4,5-dimethylaniline
EP0245774A2 (en) * 1986-05-10 1987-11-19 BASF Aktiengesellschaft Process for the manufacture of ribitylxylidine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4271290A (en) * 1978-06-15 1981-06-02 A.E.C. Societe De Chimie Organique Et Biologique 3,4-Xylidine-N-ribityl
EP0020959A1 (en) * 1979-06-08 1981-01-07 MERCK PATENT GmbH Process for the preparation of riboflavin
US4355158A (en) * 1979-06-08 1982-10-19 Merck Patent Gesellschaft Mit Beschrankter Haftung Process for the preparation of riboflavin
US4360669A (en) * 1980-08-08 1982-11-23 Basf Aktiengesellschaft Preparation of N-(D)-ribityl-2-phenylazo-4,5-dimethylaniline
EP0245774A2 (en) * 1986-05-10 1987-11-19 BASF Aktiengesellschaft Process for the manufacture of ribitylxylidine
EP0245774A3 (en) * 1986-05-10 1988-08-10 Basf Aktiengesellschaft Process for the manufacture of ribitylxylidine
US4806686A (en) * 1986-05-10 1989-02-21 Basf Aktiengesellschaft Preparation of ribitylxylidine

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